Linked Life Data

20188226

Source:http://linkedlifedata.com/resource/pubmed/id/20188226

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-5-24
pubmed:abstractText
The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administration, we administered a low dose of the transient osteoclast inhibitor salmon calcitonin (sCT) to young rats receiving an anabolic PTH regimen. Co-administration of sCT significantly blunted the anabolic effect of PTH as measured by peripheral quantitative computer tomography (pQCT) and histomorphometry in the femur and tibia, respectively. To determine gene targets of sCT, we carried out quantitative real time PCR and microarray analysis of metaphyseal samples 1.5, 4 and 6.5h after administration of a single injection of PTH, sCT or PTH+sCT. Known targets of PTH action, IL-6, ephrinB2 and RANKL, were not modified by co-administration with sCT. Surprisingly, at all time points, we noted a significant upregulation of sclerostin mRNA by sCT treatment, as well as down-regulation of two other osteocyte gene products, MEPE and DMP1. Immunohistochemistry confirmed that sCT administration increased the percentage of osteocytes expressing sclerostin, suggesting a mechanism by which sCT reduced the anabolic effect of PTH. Neither mRNA for CT receptor (Calcr) nor labeled CT binding could be detected in sclerostin-enriched cells differentiated from primary calvarial osteoblasts. In contrast, osteocytes freshly isolated from calvariae expressed a high level of Calcr mRNA. Furthermore immunohistochemistry revealed co-localization of CT receptor (CTR) and sclerostin in some osteocytes in calvarial sections. Taken together these data indicate that co-treatment with sCT can blunt the anabolic effect of PTH and this may involve direct stimulation of sclerostin production by osteocytes. These data directly implicate calcitonin as a negative regulator of bone formation through a previously unsuspected mechanism.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1873-2763
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1486-97
pubmed:meshHeading
pubmed-meshheading:20188226-Animals, pubmed-meshheading:20188226-Bone Morphogenetic Proteins, pubmed-meshheading:20188226-Calcitonin, pubmed-meshheading:20188226-Cells, Cultured, pubmed-meshheading:20188226-Computational Biology, pubmed-meshheading:20188226-Extracellular Matrix Proteins, pubmed-meshheading:20188226-Female, pubmed-meshheading:20188226-Femur, pubmed-meshheading:20188226-Genetic Markers, pubmed-meshheading:20188226-Humans, pubmed-meshheading:20188226-Immunohistochemistry, pubmed-meshheading:20188226-Interleukin-6, pubmed-meshheading:20188226-Mice, pubmed-meshheading:20188226-Mice, Inbred C57BL, pubmed-meshheading:20188226-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:20188226-Osteocytes, pubmed-meshheading:20188226-Parathyroid Hormone, pubmed-meshheading:20188226-Phosphoproteins, pubmed-meshheading:20188226-Rats, pubmed-meshheading:20188226-Rats, Sprague-Dawley, pubmed-meshheading:20188226-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20188226-Tibia
pubmed:year
2010
pubmed:articleTitle
Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes.
pubmed:affiliation
Department of Medicine at St. Vincent's Hospital, St. Vincent's Institute and University of Melbourne, Fitzroy, 3065, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural